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FLASH GENE

Symbol

WWTR1

contributors: mct/npt/pgu - updated : 23-02-2017

HGNC name	WW domain containing transcription regulator 1
HGNC id	24042

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015472 7 - 5135 NP_056287 - 400 - 2008 18568018 NM_001168278 8 - 5052 NP_001161750 - 400 - 2008 18568018 NM_001168280 7 - 4999 NP_001161752 - 400 - 2008 18568018

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system uterus       Homo sapiens Adult

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining endometrium     Homo sapiens Adult

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a PDZ-binding motif

HOMOLOGY

Homologene

FAMILY

CATEGORY

protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,nucleolus

basic FUNCTION	enhancing GLIS3-mediated transcriptional activation, indicating that WWTR1 functions as a coactivator of GLIS3
	functioning as a modulator of several transcription factors
	14-3-3 binding protein, which modulates mesenchymal stem cell differentiation and plays a critical role in the migration, invasion, and tumorigenesis of breast cancer cells
	transcription coactivator that modulates mesenchymal differentiation and development of multiple organs
	potential function as an important target of the Hippo pathway in regulating cell proliferation tumorigenesis
	functions as a novel transcriptional modulator of myogenic differentiation by promoting MYOD1-mediated myogenic gene expression
	transcriptional coactivator involved in the differentiation of stem cell as well as the development of multiple organs
	oncogene and has an important role in tumorigenicity of non-small cell lung cancer cells
	fundamental role of the transcriptional regulators YAP1 and WWTR1 as downstream elements in how cells perceive their physical microenvironment
	promotes breast cell growth partially through protecting KLF5 from WWP1-mediated degradation and enhancing KLF5 activities
	its activity is associated with tumor differentiation and prognosis
	required for self-renewal and tumor initiation of breast cancer cells
	regulates mesenchymal differentiation in malignant glioma

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

	component of the novel Hippo-LATS tumor suppressor pathway
	downstream effector of the Hippo pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	interacts with and functions as a coactivator of GLIS3 (GLIS3 and WWTR1 are part of overlapping transcription regulatory networks that play a critical role in the maintenance of normal renal architecture and function)
	physically interacts with MYOD1 through the WW domain and activates MYOD1-dependent gene transcription
	overexpression of AMOT and AMOTL1 caused cytoplasmic retention of WWTR1 and suppressed its transcriptional outcome such as the expression of CTGF and CYR61
	YAP1/WWTR1 interaction are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry
	NEK1 phosphorylates WWTR1 at a site essential for the ubiquitination and proteasomal degradation of PKD2
	in epithelial cancer cells, SCRIB is an upstream activator of the Hippo pathway leading to WWTR1 inhibition
	modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation
	BMP4 is a mediator of WWTR1-induced cell migration (WWTR1induces BMP4 transcription through the TEAD family of transcription factors, which mediate BMP4 promoter activation through binding to TEAD response element 1)
	ARHGEF7 is a key component that links the Hippo kinase cassette to YAP1/WWTR1 in response to multiple upstream Hippo pathway activators
	actin remodelling factors LIMK2 and TESK1 are key players in the ciliogenesis control network in which YAP1/WWTR1 and directional vesicle trafficking are integral components
	interaction between LEF1 and WWTR1 is crucial for the osteoblastogenic activity of WNT3A and LEF1 and WWTR1 contribute to the cooperative effect of WNT3A and BMP2 on osteoblast differentiation through association with RUNX2
	WWTR1 constitutes a key mechanistic link through which PKD1 mediates its physiological functions

cell & other

REGULATION

Phosphorylated by

NEK1

Other

phosphorylated by LATS1 tumor suppressor kinase, a key component of the Hippo pathway, whose alterations result in organ and tissue hypertrophy

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in approximately 20 p100 of breast cancer samples constitutional     --over   in placentas of preeclampsia and HELLP syndrome tumoral fusion       WWTR1-CAMTA1 fusion in all epithelioid hemangioendothelioma tested from bone, soft tissue, and visceral location (liver, lung) in keeping with a unique and specific pathological entity tumoral     --over   in non-small cell lung cancer (NSCLC) tumoral     --over   in high-grade breast cancers constitutional     --low   during decidualization

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer lung   may present a novel target for the future diagnosis, prognosis and therapy of lung cancer

ANIMAL & CELL MODELS